In Malawi, cervical cancer is the most frequent cancer among women of reproductive and economically important age (45.4% of female cancers) and an 80% mortality. Numbers are projected to increase over the next 2 decades as improvements in other areas of health (eg treatment for HIV) increase length of life. There is no national programme for cervical cancer prevention through immunisation or screening and many women now survive childbirth only to die later of preventable cervical cancer. Inadequate access to treatment, ostracisation of women with severe symptoms of cervical cancer, and limited palliative care services are additional features.

We received funding from the Scottish Government International Development Fund for Malawi (2013-2016) to set up a sustainable programme of cervical cancer reduction in Nkhoma Hospital and 10 surrounding health centres. The project is jointly led by Professor Heather Cubie, Consultant Clinical Scientist in NHS Lothian until recently / Honorary Professor, Global Health Academy, University of Edinburgh and by Dr Christine Campbell, Senior Research Fellow, Centre for Population Health Sciences, University of Edinburgh. The principal clinicians are Sr. Hilary Brown and Dr Graeme Walker from NHS Lothian who participated in ALSO courses (Advanced Life-Saving in Obstetrics) in Malawi a few years back and others from round Scotland have helped / are helping for short periods through sabbatical or unpaid leave.

The Scottish and Nkhoma teams, October 2013

In the first two years of the project, our Malawian colleagues have provided information on the value of cervical screening to 4 Traditional Authorities and 84 Group Village Headmen and obtained their permission to speak to around 30,000 people in the region. In addition, a potential 120,000 (50% of the population) has been reached by local radio broadcasts. Twenty-four Malawian healthcare professionals (mainly midwives and clinical officers) have been trained to provide cervical screening using a procedure called VIA (visual inspection with acetic acid) and treatment of early lesions using cold coagulation. Case load is audited and competency of each provider is assessed by Scottish clinicians using similar standards to the UK.

Talk to women to explain what would happen in VIA clinic, Nkhoma Hospital

October 2013

In the new outside classroom, October 2014

Over 7000 women have had their first-ever cervical screen. Those with early signs of abnormality have been offered treatment and 75% received it the same day. At the start of the project, a number of women said they would need to ask permission from their husbands to receive treatment but this is no longer a big issue. Hopefully this is because the information messages have reached the whole population, men and women, giving women a sense of empowerment. Two-thirds have returned for follow-up visits, despite this being considered difficult to achieve.

Sadly, the VIA clinics still see too many women with cancers which are too advanced for immediate treatment. There is little Malawi can offer in terms of chemo- or radiotherapy, but the project does ensure that these women have their diagnosis fully explained and are offered surgery or palliative care where appropriate.

The project now has daily clinics in Nkhoma Hospital and weekly clinics in 5 surrounding health centres, some Government and some CHAM. Year 3 of the project will extend to weekly clinics in 5 more health centres and consolidate training to allow sustained service. We are currently looking for further funding to extend the ‘hub and spokes’ model to additional hospitals and their health centres.

Surgeons have long felt that the importance of surgery has been lost in past efforts to impact on global health issues. The Lancet Commission on Global Surgery seeks to address deficiencies in surgical and anaesthetic care, provide evidence and solutions for achieving health, as well as welfare and economic development through the strengthening of surgical health systems in Low and Middle income Countries (LMIC).

Twenty five commissioners have worked for almost 2 years consulting extensively in over 100 countries in 6 continents. Their report may not please all but is a significant achievement. Surveys, epidemiological studies, estimates, audits and mapping programmes helped to provide evidence and to highlight further disparities in surgical care through 5 key messages at their recent London and Boston launches:

143 million additional surgical procedures are needed each year to save lives and prevent disability. Only 6% of 313 million procedures that are undertaken worldwide annually, are performed in the poorest countries.

100% protection against impoverishment from out of pocket payments for surgical care.

100% protection against catastrophic expenditure from out of pocket payments for surgical care.

Some might see these as challenging for some developed countries so how can these objectives be met in developing countries where increasing funding of health care still results in disparities.

We know that targeting specific health care issues through philanthropic support in the developing world has brought about mixed success. Numerous philanthropists and charities have stumbled in attempting to deliver sustainable solutions when investing in facility or service. Outreach programmes from well intended overseas surgical teams may actually impact adversely on the very environment that they hope to support. Essential emergency provision of surgical care may be compromised when, for example, limited facility is set aside for the orchestrated elective missionary surgery. The conditions or surgical pathology targeted or technology being shared may seem entirely appropriate to the visiting team but may be largely irrelevant to the needs of the local population.

Investment in infrastructure may seem to produce a tangible legacy for the donor but it is challenging to maintain such quality facilities when these are seen by some as a source of material to be plundered to support their families in desperate financial need. Furthermore, some initiatives have been been criticized for focusing too narrowly on the capacity of science and in neglecting the importance of economic, social, and political factors. Such surgical initiatives require significant funding and need to be considered in parallel with improvements in public health, education and the health system. Pressurised surgical services dealing with trauma in the developing world might rather welcome greater health and safety regulation, improvements in street lighting, better maintained roads and greater driver regulation.

So where to start? Records often do not exist so reliable surgical audits or death rate statistics for surgery do not exist in LMIC. Investment in information technology is limited in most developing countries but finance is required to obtain key information that would identify clearly the needs of surgical services in the LMIC. GlobalSurg is a collaboration supported by Clinical Surgery at the University of Edinburgh (http://globalsurg.org/get-involved/). The group is currently using an international network of training and qualified surgeons to study variation in outcome of emergency intra-abdominal surgery across various clinical settings. It will determine whether globally relevant quality improvement strategies are needed within acute surgical units. This project would serve to provide much needed information in an area of acute surgical care and will allow development of regional, national and international surgical networks. The group recently published on the benefits of these networks in the Lancet. There is no reason why the group cannot establish key global studies, including the opportunity for randomised trials.

Humanitarian and global surgical outreach programmes have been supported by surgical colleagues in Edinburgh at considerable personal social and psychological sacrifice. Such direct support has undoubtedly had significant impact on the lives of those affected by conditions including those arising from complications of obstructed labour. The social stigmata attached to this condition are considerable and the repair transforms the patient’s existence. And yet, the procedure to correct a vesicovaginal fistula is categorized as a ‘can do’ rather than a ‘must do’ surgical procedure. Where should the priorities lie when the challenge is so immense? How can such outreach programmes deliver a legacy in a developing country?

The target set by the Commission that 100% of countries should have at least 20 surgical, anaesthetic, and obstetric physicians per 100,000 population is formidable. We have experience supporting surgical training in Malawi which produces some 100 medical graduates per year. However, for a population of 17 million people, there are currently only some 15 trained surgeons in practice since many move overseas when they are exposed to the opportunities that exist for well-trained doctors in the developed world. The Lancet Commission requirement by 2030 is projected at 60 specialists per 100,000 population. It is difficult to imagine where the additional 10,000 or so specialists will emerge for Malawi without substantial investment.

Scotland has a strong tradition of investing in education on Africa. Gordon Brown as UN Special Envoy for Global Education, and through the Office of Gordon and Sarah Brown, has promoted and initiated education programmes in Africa. Edinburgh University has invested strongly in postgraduate educational initiatives that have benefited LMIC. The huge success of our own surgical distance learning programmes has allowed us to support more trainees from these countries.

Our surgical Masters programmes currently have over 450 students enrolled in 40 different countries. In 2009, the Scottish Government and J&J/Ethicon supported the University of Edinburgh and the Royal College of Surgeons of Edinburgh to deliver free postgraduate educational support to training surgeons in Malawi. Since then, the first three students have graduated from the three-year distance learning course which supports the educational and professional needs of the young training surgeon. Six more Malawian trainees are currently in the programme. Surgical trainees have been supported without the need to remove them from the area of greatest need. The programme content adds value to their in-the-workplace training and allows the young surgeon to attend to local service needs. We are also aware that educational resource has been extended to medical assistant practitioners who are a vital link in the surgical care chain.

The Lancet Global Commission has ensured that surgery can no longer be overlooked as a health need for the world’s poorest people. The Commission has set itself ambitious targets but no one initiative will address the current unmet need. Better global surgical and anaesthesia care will only be realised through increased investment in human and physical resources. Early and urgent domestic and external investment in surgical and anaesthesia care is needed to realise these returns. Our group sees itself as being in a strong position to invest in the postgraduate education of the surgical workforce in these countries.

Similarly, research, monitoring, and assessment will have to play an increasing and crucial part in the future of global surgical and anaesthesia care. There is a paucity of scientific rigor around implementation science, and an absence of globally accepted surgical metrics which have contributed to past neglect of surgical and anaesthesia care within global health. A commitment to better understand the problems and solutions should be a priority for those dedicated to improvement of surgical and anaesthesia care worldwide. We will continue to invest primarily in the training surgeons in these LMIC through postgraduate education. In this way, we should empower the very body that can engineer change locally so that we might yet see some practical light at the end of a very long tunnel.

Sun Tzu, a Chinese military philosopher in the 6th century BC, said “ if you know your enemy and yourself, you will not be imperiled in hundred battles”.

If not taken in literal terms, it would suggest that learning more about the humanity and livestock’s arch enemy Tuberculosis (TB), with whom we have been battling for millennia, can only arm us all the better for the fight. As part of this battle, The University of Edinburgh has long been contributing to the research and development arm of the World Health Organisation’s “Stop TB Global Strategy”.

The WHO has achieved the 2015 Millennium Goal of halting and reversing the incidence of the disease. Despite this great acheivement, in 2013 alone the WHO registered 9 million cases of TB, half a million of which succumbed to the disease. Horrifyingly this latter number loosely translates to four super jumbo jets crashing every day for the entire year. Going forward to 2035, the WHO has set yet more ambitious goals to end the global TB epidemic with corresponding targets of 95% and 90% reduction in TB deaths and incidence respectively.

Knowing your enemy

In order to achieve this mighty aim, now more than ever, it is critical for the definitive diagnostics to not only reveal the mycobacterial species but also the genotype. The majority of cases of human TB are caused byMycobacterium tuberculosis, however a small, but significant geographically-limited, proportion is due toMycobacterium bovisthe causative agent of bovine tuberculosis. The latter is what is commonly referred to as zoonotic tuberculosis. The current statistics shows that when considered as a proportion of the global TB burden, zoonotic tuberculosis accounts for a small proportion however, if reported in absolute terms it translates to between 95,000 and 150,000 cases of which 15% succumb to this disease form globally. It is noteworthy that 9 out of the 22 high-burden TB countries are responsible for ~70% of the global zoonotic TB cases.

Vaccination as a defence against infection

In general, vaccination is an effective method of controlling infectious diseases. The BCG vaccine, developed agianstM. bovis, is the most widely administered TB vaccine in the world. However its varied efficacy globally has always been a challenge to the TB control strategy. If the endemic population of infective bacteria is different from that contained in the vaccine, this can lead to vaccine failure. Vaccines that target a narrow range of phenotypes may not offer sufficient prevention against infections in settings where multiple different strains of the infective agent may be present.

This is particularly relevant to areas where several different strains ofM. bovisare prevalent, and where the TB burden is correspondingly high. It is also reasonable to argue that some of the TB treatment failures in these areas are likely due to species and genotypes un-accounted for in the treatment protocols. Thus it is critical to document the diversity ofM. bovis, and use this data to increase the phenotypic range in novel vaccines, thereby improving patient immunity.

Sequencing the genomes of the bacteria that cause TB

The currently documented genotypes ofM. bovisin high-burden settings lack “granularity” because they are based on PCR methods that target less than 0.005% of the genome. It is therefore likely that niche and host-specific polymorphisms that are critical for population-based vaccine implementation, are left unused in determining these genotypes.

This disparity in genotype diversity and breadth of target phenotype is likely part of the reasons why the efficacy of BCG vaccination is lowest in Africa. A solution to this comes in the form of whole genome SNPs based genotyping, which offers high definition genotyping power capable of revealing subtle niche and host specific diversity.

Large international collaboration fighting the disease

Researchers from the University of Edinburgh are now part of a large international collaboration that will sequence and genotype 254 isolates ofMycobacterium bovisfrom eight African high burden countries.

The new data the team generates will be made freely available for researchers and industry involved in TB vaccine, diagnostics and therapeutics development. By piecing together more and more information about the strains of Mycobacteria causing TB in different areas, researchers will generate the ammunition needed to finally defeat TB.

It states boldly that “The world is embarking on a Fast-Track strategy to end the AIDS epidemic by 2030”.

It envisages that if the world scales up its HIV prevention and treatment programmes and reaches certain fast-track targets or goals, it will manage to prevent almost 28 million new infections and more crucially “end the AIDS epidemic as a global health threat by 2030”.

The report points to a number of “fast-track targets” that need to be achieved in the next five years by 2020. These optimistic targets include: attaining a 90-90-90 target, i.e. 90 percent of people with HIV knowing their status, 90 percent of those who know their status being on treatment, and then 90 percent of those on treatment suppressing the virus. For the year 2030, this goal goes up to 95-95-95. New infections will be reduced by 75 percent to 500,000 by the year 2020, and then to 200,000 by 2030. And, it points to the overarching goal of zero discrimination and zero tolerance for both years—2020 and 2030.

However, to achieve this monumental, yet attainable goal, the report cautions that “countries will need to use the powerful tools available, hold one another accountable for results and make sure that no one is left behind”.

We at the HHRD Network believe that the commitment to human rights will provide the bedrock of the AIDS response, and that human rights will need to remain in the fore front of all efforts. Moreover, that there is a need for a sustained and continued investment to build and promote the capacity of health systems all over the world, but particularly in the context of developing countries and forced migration. We need to consider on how best we can attain the theme of World AIDS Day 2014 to “Focus, Partner, Achieve: An AIDS-free generation – to highlight the need to for governments and health officials, NGOs and individuals to address AIDS prevention and treatment”. And, finally, the “fast-track targets” need to be held closely by all players across the globe if we are to “not just bend the epidemic trajectory, but to break it irreversibly”.

What happens afterwards? This apocalyptic question is one that is integral to all forms of intervention in human and animal diseases. This is particularly important in cases where the intervention occurs at a national scale. My research group has been asking this question in relation to the current global efforts to control worm (helminth) infections which significantly impact on the health and development of children. Specifically, we work on bilharzia (urinary schistosomiasis) an important, but neglected infectious disease caused by the blood fluke Schistosoma haematobium. Although we hear occasional reports of tourists infected during visits to resorts in endemic areas, bilharzia is typically a disease of poverty due its association with poor sanitation and unsafe water. People become infected when they come into contact with the infective stage in freshwater after it has been released by freshwater snail- hence the other name of the disease- snail fever. The disease affects over 100 million people, mainly in Africa. Children carry the heaviest burden of infection; as a result, they experience bladder and kidney disorders, stunted growth and poor development.

Current global initiatives from Partners of Parasite Control including the World Health Organization (WHO), Bill and Melinda Gates Foundation, UNICEF, Schistosome Control Initiative and the World Bank are advocating regular school-based de-worming interventions to reduce the development of morbidity, promote school-child health and improve cognitive potential of the children. Children are treated with the antihelminthic drug praziquantel. Over the past decade, there has been a concerted global effort to control bilharzia, galvanised initially by the Millennium Development Goal (MDG) 6 to combat HIV/AIDS, malaria and other diseases by 2015 and the World Health Assembly resolution 54.19 to treat at least 75% of all school-age children at risk of schistosomiasis by 2010. The most recent schistosomiasis resolution, World Health Assembly resolution WHA65.21 passed in 2012 is advocating for the elimination of schistosome transmission and the WHO Schistosomiasis Strategic Plan 2012-2020 sets out its vision of for a world free from schistosomiasis. This represents a real drive at the global scale not previously seen, to control this important disease of childhood.

Millions of school children in Africa are currently being treated with this drug resulting in significant health improvements. In several countries where the control programmes are currently being implemented, they are typically running for 5 years. The questions we are asking is what will happen to 1) the children who have been treated, 2) the rest of the population that has not been treated and 3) the parasites? The overall, long-term outcome of these treatment programmes for human health is believed to be good- but what evidence do we have for this? In my research group, we are interested in the long-term consequences of praziquantel treatment. Our studies and those of others have shown that the effects of praziquantel treatment go beyond the transient reduction of infection intensity and morbidity. Treatment with the antihelminthic also reduces future pathology and induces immune responses protective against re-infection by the parasites. What will be the effect of the 5-year treatment programmes on the host immune system and overall health? Experimental studies of the regulation of the immune system suggest that treatment of helminth infection results in susceptibility/worsening of immune disorders (explained through the hygiene hypothesis). What is the relevance of these studies to human helminth infection? What are the long-term health implications in children treated through these national treatment programmes? Similar to malaria, people exposed to schistosome parasites develop natural acquired immunity to the parasites following repeated infection with the parasites. What is the consequence of praziquantel treatment on schistosome immunity and disease, decades after cessation of the control programmes? Providing answers to these questions is critical for informing strategic planning for ministries of health and prioritisation of resources as well as formulating /directing global health policy.

These really interesting scientific questions and the potential impact of the findings for human health are the drivers of research for Dr Francisca Mutapi and her group, the Parasite Immuno-epidemiology Group, at the University of Edinburgh.

As part of a study to analyse changes in global health priorities at the global level of the resolutions adopted at the World Health Assembly – the decision making body of the WHO – the relative neglect of endemic zoonotic diseases has been highlighted. This work has recently been published in PLOS NTDs, and has received widespread media attention.

The eight diseases of interest (anthrax, bovine tuberculosis, brucellosis, cysticercosis, echinococcosis, human African trypanosomiasis (HAT), leishmaniasis, rabies) are part of the group termed Neglected Zoonotic Diseases (NZDs) at an international meeting in 2005, so called as they are “not adequately addressed” at national and international levels. Zoonotic diseases are defined as diseases that are transmissible between humans and animals.

In the last decade, the Neglected Tropical Diseases (NTDs) have received increased global attention, and recent events celebrated the increased advocacy and control that has occurred. The research highlighted that these diseases have received relatively little attention at the global policy level, living up to their neglected title. In developing countries where these diseases remain endemic and resources are limited, the control of these diseases is limited as other high profile diseases are prioritised.

Some of the diseases have high fatality and cause a high number of deaths globally each year. For example, rabies causes an estimated 60,000 deaths worldwide, yet this disease remains neglected despite evidence that the disease can be effectively controlled through dog vaccination.

Neurocysticercosis is the greatest cause of preventable epilepsy worldwide, causing an estimated 30% of the 17 million cases of epilepsy in areas where the causative parasite is endemic. This disease can be controlled through sanitation and improved pig husbandry, and improved diagnosis of human infection, requiring a multi-sector approach.

Following the London Declaration on NTDs, there has been increased focus on NTD control. Of the NZDs, only leishmaniasis and HAT are included in the ten diseases which are the focus of the declaration, meaning that the other diseases are not benefitting from the increased Research and Development and drug donations that the other NTDs are experiencing as a result of the declaration. This study highlighted three diseases in particular that are not included in the WHO NTDs. Anthrax, brucellosis and bovine tuberculosis have therefore not received the increased attention that the other NTDs have seen. Upon the inception of the WHO in 1948, around twenty zoonotic diseases were determined to be diseases of priority in the WHO, including bovine tuberculosis and brucellosis. Despite this, there have not been any resolutions adopted for these diseases since 1950. For these diseases, effective and simple control methods exist, meaning that they are no longer endemic in many developed countries. It is therefore astonishing to many that they remain neglected.

It seems that these diseases are particularly neglected due to the complexities of controlling diseases that affect both humans and animals, and the required communication and collaboration between human and animal health sectors, both at community and ministerial levels, that is sometimes lacking. This despite the dual benefits that would be received by both human and animal health sectors upon increased effective control methods.

The international attention that has been received following the publication of this research may be indicative that the neglect of these diseases – some of which are well known and well controlled in some countries – may be something which is surprising, but that there is desire to reduce this neglect and therefore the deaths that occur as a result. In order to reduce this neglect, we must see increased cooperation and communication between human and animal sectors at all levels, and efforts to increase the advocacy for the control of these diseases.

Ms Hayley Mableson is in the final stages of completing a PhD from the University of Edinburgh. Her research to date has focussed on global health advocacy and its application, with particular emphasis on the neglected tropical and zoonotic diseases.

1981 saw the first description of AIDS cases in the USA. There are now over 100,000 people living with HIV in the UK and around 34 million people worldwide. In 2011, an estimated 1.7 million people worldwide died from HIV related causes. In the UK, around 1 in 5 patients living with HIV are not aware of their diagnosis; more efforts should be done to identify them so that they can benefit from antiretroviral treatment and improved health. Treated early, patients with HIV can look forward to an almost normal life span.

Despite extensive research, there is no effective vaccine for treatment or prevention of HIV infection. Treatment is effective and is required lifelong as at present there is no cure. Antiretroviral therapy fails to cure HIV infection because latent proviruses persist in resting CD4+ T cells.

Although the international response to HIV epidemic has not been rapid, more than half of people eligible for ART in low and middle income countries were receiving ART for the first time in 2011.

Lifelong therapy means that patients are exposed to potential drug toxicity for a prolonged period. People with HIV are living longer; the proportion of patients aged 50 and older are an increasing proportion of the population of persons living with HIV in the UK. Older people with HIV/AIDS face both HIV/AIDS-related and age-related co-morbidities, such as hypertension, chronic pain, hepatitis, and arthritis, which are associated with poorer physical, mental, and social wellbeing.

The global HIV epidemic is one of the most formidable challenges to life and human dignity; it undermines social and economic development worldwide. Efforts at eradicating HIV must be maintained by finding a cure for those who are already infected and an affordable and effective vaccine to prevent new infections.